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Myeloma

Relationship between elevated immunoglobulin free light chain and the presence of IgH translocations in multiple myeloma

Leukemia volume 24, pages 1498–1505 (2010)Cite this article

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Abstract

Elevated immunoglobulin free light chain (FLC) level and abnormal FLC ratio are commonly seen in multiple myeloma (MM) and have prognostic implications. We hypothesized that presence of immunoglobin heavy chain (IgH) translocations leads to unbalanced production of light chains and more extreme abnormalities of FLC, and may explain the prognostic value of FLC. We studied 314 patients with newly diagnosed MM enrolled in a phase III trial, in whom results of fluorescence in situ hybridization testing and data on serum FLC levels were available. Cytogenetic analyses and FLC estimates were performed on stored samples and results were correlated with clinical data. The median ratio (FLC ratio) and the absolute difference (FLC diff) between the involved and uninvolved FLC were higher among those with IgH translocations, especially t(14;16). In multivariate analysis, the prognostic value of FLC estimates on progression-free and overall survival were independent of high-risk IgH translocations t(4;14) and t(14;16). A combination of the risk factors; either abnormal FLC estimate and/or the presence of high-risk IgH translocation, achieved better prognostic stratification. We conclude that patients with IgH translocations have higher FLC levels and abnormal ratios, but the prognostic effect of FLC is only partially explained by translocation status. A system including both these risk factors allows better prediction of outcome.

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Acknowledgements

This study was coordinated by the Eastern Cooperative Oncology Group (RL Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, and CA13650; by Grants from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

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Authors and Affiliations

  1. Division of,

    S Kumar, A Dispenzieri, R DeGoey, K Henderson, R A Kyle, P R Greipp & S V Rajkumar

  2. Hematology, Mayo Clinic, Rochester, MN, USA

    S Kumar, A Dispenzieri, R DeGoey, K Henderson, R A Kyle, P R Greipp & S V Rajkumar

  3. Department of,

    L Zhang

  4. Biostatistics, ECOG, Boston, MA, USA

    L Zhang

  5. Department of,

    S Van Wier & R Fonseca

  6. Hematology, Mayo Clinic, Scottsdale, AZ, USA

    S Van Wier & R Fonseca

  7. Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    J A Katzmann & M Snyder

  8. Dartmouth Medical School, Lebanon, NH, USA

    E Blood

  9. Department of Immunology, Birmingham University Medical School, Birmingham, UK

    A R Bradwell

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Correspondence to S Kumar.

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SK, AD, RF, LZ, EB, MS, RD, KH, SV, RAK, MO, PRG declare no conflict of interest. ARB is an employee of the Binding Site. JAK receives reagents from the Binding Site.

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Kumar, S., Zhang, L., Dispenzieri, A. et al. Relationship between elevated immunoglobulin free light chain and the presence of IgH translocations in multiple myeloma. Leukemia 24, 1498–1505 (2010). https://doi.org/10.1038/leu.2010.128

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